*Brain bleeding or bleeding requiring transfusion
Efficacy Endpoints: Mortality, Primary or Secondary myocardial infarction
Harm Endpoints: Major bleeding, Minor bleeding
Narrative: 'Acute coronary syndrome' in this review includes cardiac conditions believed to be caused by arteries partially or completely occluded due to a combination of longstanding plaques in artery walls and new tears in the innermost lining of the artery (the tears are caused by plaques poking through). The blood typically misinterprets these tears as bleeding and forms a clot where the tears are, clogging the artery. Heparin inhibits clotting which seems intuitively like it would help but by the time the patient has symptoms like chest pain a clot has already formed, so it's unclear how much this can help. In addition, anything that inhibits clotting can lead to bleeding.
Eight randomized control trials of >3100 patients are included. Heparin did not reduce deaths or non-fatal heart attacks. There was no difference in major bleeding in the included studies, though minor bleeding events increased by 7.5%, or 1 in every 17 subjects.
Caveats: Heparin did not measurably prevent deaths but because so few people died in either group the review did not have the ability to detect very small differences. Notably, the Cochrane review concludes a 3% absolute benefit for reducing nonfatal heart attacks in the first week after the initial acute coronary syndrome, however this benefit is gone at 30 days of follow-up and at 3-6 months. After the first week, any reduction in heart attacks is neutralized as subjects in the heparin groups rapidly 'catch up' by suffering more heart attacks than those in the groups receiving placebo.
The Cochrane review reports early studies of heparin versus placebo for ACS. Later studies are more diligent and transparent in their reporting of major bleeding events. These later studies appear to represent an experience that is much closer to the community experience and suggest a roughly 4-5% major bleeding rate (above and beyond aspirin) with any heparin.1 Therefore it is likely that the true NNH for heparins in ACS is roughly 20 to 25 for major bleeding events. We added this as a quantifiable harm because we find the proposition that heparin has no effect on major bleeding events to be implausible, and the later study results are the highest quality that we could identify. Actual bleeding event rates may be higher, though they seem unlikely to be lower.
Author: Koustav Mukherjee, MD, Ashley Shreves, MD and David Newman, MD
Published/Updated: January 19, 2010
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